Table 1.
Nominated causal genes at top TG/HDL risk loci
| Gene | Lead SNP | Chr:Pos | EA | OA | EAF | Beta (SE) | p-value | Boost score | tsex-dimorphic | p-valuesex-dimorphic | Top Causal SNP | SNP-gene annotation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LPL | rs271 | 8:19813702 | A | G | 0.146 | −0.125 (0.003) | 3.58e-307 | 50.353 | −2.189 | 2.86e-02 | rs268 | Exonic (p.Asn318Ser) |
| ANGPTL4 | rs116843064 | 19:8429323 | A | G | 0.019 | −0.248 (0.007) | 1.03e-189 | 49.807 | −3.802 | 1.43e-04 | Exonic (p.Glu40Lys); Regulatory variant | |
| IRS1 | rs2943645 | 2:227099180 | T | C | 0.646 | 0.048 (0.002) | 2.48e-85 | 2.056 | 3.240 | 1.20e-03 | Fine-mapped eQTL | |
| APOB | rs533617 | 2:21233972 | C | T | 0.040 | −0.103 (0.005) | 5.14e-67 | 5.480 | −0.803 | 4.22e-01 | Exonic (p.His1923Arg) | |
| VEGFA | rs6905288 | 6:43758873 | A | G | 0.568 | 0.039 (0.002) | 8.54e-63 | 6.813 | 0.106 | 9.16e-01 | Regulatory variant | |
| KLF14 | 7:130438531_CTTTTTT_C | 7:130438531 | C | CTTTTTT | 0.516 | −0.037 (0.002) | 2.50e-55 | 12.202 | 7.959 | 1.73e-15 | Nearest gene | |
| COBLL1 | rs79953491 | 2:165555539 | G | A | 0.120 | −0.05 (0.003) | 2.78e-44 | 9.028 | 3.251 | 1.15e-03 | Promoter | |
| PLCB3 | rs71468663 | 11:64018104 | AC | A | 0.046 | 0.067 (0.005) | 1.23e-32 | 3.241 | −0.994 | 3.20e-01 | Nearest gene | |
| RSPO3 | rs6916318 | 6:127435106 | T | A | 0.531 | 0.028 (0.002) | 1.42e-32 | 5.971 | −5.274 | 1.34e-07 | rs577721086 | Exonic (5_prime_UTR_variant) |
| ARID1A | rs114165349 | 1:27021913 | C | G | 0.023 | 0.092 (0.007) | 3.13e-32 | 4.273 | −1.461 | 1.44e-01 | Nearest gene | |
| NTAN1 | rs11075253 | 16:15148646 | A | C | 0.297 | −0.03 (0.002) | 1.00e-30 | 3.781 | −0.415 | 6.78e-01 | Promoter; Fine-mapped eQTL | |
| PCCB | rs684773 | 3:135956305 | C | A | 0.767 | 0.031 (0.002) | 6.27e-30 | 2.487 | −0.741 | 4.59e-01 | Regulatory variant | |
| NEK4 | rs6800707 | 3:52516293 | G | C | 0.810 | 0.031 (0.003) | 5.37e-25 | 3.775 | −2.656 | 7.90e-03 | rs11235 | Exonic (3_prime_UTR_variant) |
| PLA2G12A | rs114816312 | 4:110638824 | T | C | 0.008 | 0.139 (0.012) | 6.43e-25 | 3.737 | 0.681 | 4.96e-01 | rs41278045 | Exonic (p.Cys131Arg) |
| PLA2G6 | rs200725415 | 22:38575498 | C | CT | 0.440 | −0.024 (0.002) | 9.26e-25 | 3.950 | −2.334 | 1.96e-02 | Nearest gene | |
| RBPJ | 4:26050450_AC_A | 4:26050450 | A | AC | 0.166 | 0.032 (0.003) | 1.01e-24 | 4.731 | −3.646 | 2.66e-04 | Fine-mapped eQTL; Regulatory variant | |
| PDE3A | rs11045171 | 12:20470199 | G | A | 0.198 | −0.029 (0.003) | 4.56e-23 | 4.616 | 1.173 | 2.41e-01 | rs4762753 | Fine-mapped eQTL |
| ACACB | rs149793040 | 12:109661672 | G | A | 0.002 | −0.262 (0.023) | 5.87e-23 | 1.906 | 0.336 | 7.37e-01 | Exonic (p.Tyr1282Cys) | |
| SNX10 | rs1534696 | 7:26397239 | A | C | 0.540 | −0.023 (0.002) | 3.93e-22 | 5.134 | 2.542 | 1.10e-02 | Fine-mapped eQTL; Regulatory variant | |
| TSC22D2 | rs62271373 | 3:150066540 | A | T | 0.060 | 0.046 (0.004) | 2.56e-20 | 5.194 | −0.016 | 9.88e-01 | Nearest gene | |
| AC022431.2 | rs60803019 | 5:55808415 | C | T | 0.065 | −0.043 (0.004) | 4.90e-20 | 3.422 | −0.853 | 3.94e-01 | rs455660 | Nearest gene |
| INSR | rs3890483 | 19:7220596 | T | G | 0.441 | 0.022 (0.002) | 5.41e-20 | 3.064 | −2.326 | 2.00e-02 | rs1799816 | Exonic (p.Val1012Met) |
| TTLL4 | rs148358468 | 2:219590348 | A | G | 0.050 | 0.047 (0.005) | 5.50e-18 | 3.488 | −0.348 | 7.28e-01 | rs116204487 | Promoter; Regulatory variant |
| TNFAIP8 | rs1045241 | 5:118729286 | T | C | 0.272 | −0.023 (0.002) | 5.53e-18 | 1.758 | 4.014 | 5.97e-05 | Exonic (3_prime_UTR_variant) | |
| RP11-1102P16.1 | rs13269725 | 8:72459889 | G | A | 0.079 | 0.037 (0.004) | 1.21e-17 | 2.402 | −3.241 | 1.19e-03 | Exonic (5_prime_UTR_variant) | |
| ADRB1 | rs2773469 | 10:115798895 | G | A | 0.735 | −0.022 (0.002) | 1.92e-17 | 2.904 | −0.204 | 8.38e-01 | Nearest gene | |
| PPARG | rs2067819 | 3:12359049 | A | G | 0.214 | −0.024 (0.002) | 2.04e-17 | 4.421 | −2.385 | 1.71e-02 | rs59447614 | Nearest gene |
| PEMT | rs11658944 | 17:17425279 | T | C | 0.057 | 0.042 (0.004) | 1.07e-16 | 3.618 | −3.067 | 2.16e-03 | Nearest gene | |
| USP3 | rs7175602 | 15:63367032 | C | T | 0.197 | 0.024 (0.003) | 5.84e-16 | 1.546 | 0.016 | 9.87e-01 | rs17184382 | Fine-mapped eQTL; Regulatory variant |
| SIPA1 | rs2306363 | 11:65405600 | T | G | 0.207 | −0.023 (0.003) | 7.64e-16 | 1.966 | −1.857 | 6.34e-02 | Exonic (5_prime_UTR_variant) | |
| KCNH2 | 7:150288766_GA_G | 7:150288766 | G | GA | 0.224 | 0.022 (0.002) | 2.39e-15 | 2.383 | −0.857 | 3.91e-01 | rs2968864 | Fine-mapped eQTL |
| CRTAC1 | rs563296 | 10:99772404 | A | G | 0.558 | 0.018 (0.002) | 2.71e-14 | 2.073 | −0.256 | 7.98e-01 | Nearest gene | |
| HNRNPK | rs296886 | 9:86592026 | G | A | 0.214 | −0.021 (0.002) | 7.79e-14 | 2.882 | 1.784 | 7.44e-02 | Nearest gene | |
| AHR | rs4410790 | 7:17284577 | C | T | 0.633 | 0.018 (0.002) | 3.71e-13 | 2.820 | −1.691 | 9.08e-02 | Nearest gene | |
| RP11-399J13.3 | rs678614 | 11:64799894 | C | A | 0.722 | −0.019 (0.002) | 7.56e-13 | 3.879 | −0.635 | 5.26e-01 | Nearest gene | |
| FARP2 | rs4675812 | 2:242395674 | A | G | 0.588 | −0.017 (0.002) | 1.53e-12 | 2.106 | 1.097 | 2.73e-01 | Nearest gene | |
| GADD45G | rs10797115 | 9:92191256 | T | C | 0.542 | 0.017 (0.002) | 1.59e-12 | 1.648 | −1.267 | 2.05e-01 | Nearest gene | |
| EYA2 | rs55966194 | 20:45599090 | G | C | 0.283 | −0.018 (0.002) | 3.59e-12 | 1.690 | 1.087 | 2.77e-01 | Nearest gene | |
| RNF168 | rs13094241 | 3:196190893 | G | T | 0.728 | −0.018 (0.002) | 9.51e-12 | 3.532 | 0.595 | 5.52e-01 | Fine-mapped eQTL | |
| VGLL3 | rs13066793 | 3:87037543 | G | A | 0.090 | −0.027 (0.004) | 1.98e-11 | 2.121 | 0.239 | 8.11e-01 | Fine-mapped eQTL; Regulatory variant | |
| CD248 | rs490972 | 11:66079786 | A | G | 0.469 | 0.015 (0.002) | 1.91e-10 | 2.400 | −0.621 | 5.35e-01 | rs1625595 | Fine-mapped eQTL |
| B3GNT4 | 12:122515547_ATTTTTC_A | 12:122515547 | A | ATTTTTC | 0.192 | 0.018 (0.003) | 1.06e-09 | 1.533 | −4.281 | 1.86e-05 | rs12827843 | Exonic (5_prime_UTR_variant) |
| ZIM2 | rs8102873 | 19:57488423 | T | C | 0.585 | 0.014 (0.002) | 1.43e-09 | 1.927 | −2.175 | 2.96e-02 | Regulatory variant | |
| AXL | rs4802113 | 19:41740895 | C | T | 0.457 | −0.014 (0.002) | 1.45e-09 | 1.884 | −1.125 | 2.60e-01 | Nearest gene | |
| RREB1 | rs35742417 | 6:7247344 | A | C | 0.184 | −0.018 (0.003) | 2.91e-09 | 1.986 | −0.358 | 7.20e-01 | Exonic (p.Ser1554Tyr); Regulatory variant | |
| UBE2K | rs145766974 | 4:39677849 | T | C | 0.569 | −0.013 (0.002) | 1.41e-08 | 2.346 | 2.409 | 1.60e-02 | rs34258469 | Nearest gene |
| QKI | rs4709746 | 6:164133001 | T | C | 0.134 | −0.019 (0.003) | 2.77e-08 | 2.129 | 0.675 | 5.00e-01 | rs7761309 | Regulatory variant |
| FGFR2 | rs878409 | 10:122999550 | A | G | 0.546 | −0.013 (0.002) | 3.39e-08 | 2.376 | 0.982 | 3.26e-01 | Nearest gene | |
| THRB | rs7640648 | 3:24313675 | G | A | 0.106 | 0.021 (0.003) | 3.63e-08 | 1.506 | 0.344 | 7.31e-01 | Nearest gene | |
| FADS2 | rs117186302 | 11:61456420 | C | T | 0.026 | −0.041 (0.007) | 4.36e-08 | 1.545 | −0.130 | 8.96e-01 | rs174566 | Nearest gene |
Fifty nominated genes at top quartile boosted TG/HDL risk loci. Each locus is defined by a lead SNP at Chr:Pos indicated, with positions in GRCh37. The effect/other alleles (EA/OA) are noted, and the effect allele frequency (EAF), Beta and standard error (SE), and GWAS p-value are in reference to the effect allele. The boost score is listed, which quantifies the difference in association of each locus between TG/HDL and TG or HDL alone, with boost score > 0 indicating increased significance in GWAS for TG/HDL compared to TG or HDL alone. The sex-dimorphic effects (tsex-dimorphic) of each locus are shown, with a positive t-statistic indicating greater significance in female-specific GWAS for TG/HDL compared to male, and the sex-dimorphic p-value (p-valuesex-dimorphic) quantifying if the difference between sexes is significant. Top causal SNPs are listed if different from the locus lead SNP, and the annotation of the lead SNP/top causal SNP for gene nomination at each locus is listed.